Reduced medial prefrontal N-Acetyl-Aspartate levels in pediatric major depressive disorder: A multi-voxel in vivo¹H spectroscopy study

There is increasing evidence of a reciprocal fronto-limbic network in the pathogenesis of mood disorders. Prior in vivo proton (¹H) spectroscopy studies provide evidence of abnormal neurochemical levels in the cingulate and dorsolateral prefrontal cortex (DLPFC) of adult subjects with major depressive disorder (MDD). We examined whether similar abnormalities occur in children and adolescents with MDD. We collected two-dimensional multi-voxel in vivo ¹H spectroscopy data at 1.5 Tesla to quantify levels of N-acetyl-aspartate (NAA), glycerolphosphocholine plus phosphocholine (GPC+PC), and phosphocreatine plus creatine (PCr+Cr) in the DLPFC, medial prefrontal cortex (MPFC), and anterior cingulate (AC) of children and adolescents aged 8-17years with MDD (n=16) compared with healthy control subjects (n=38). Analysis of covariance with age and gender as covariates was performed. MDD subjects showed significantly lower levels of NAA in the right MPFC and right AC than controls. MDD subjects also had significantly lower levels of GPC+PC in the right AC than control subjects. There were no significant differences in other metabolites in the studied regions. Pediatric patients with MDD exhibit neurochemical alterations in prefrontal cortex regions that are important in the monitoring and regulation of emotional states.